The present invention relates to measurement of electrical signals of a body of a subject and, more particularly, to measurement of electrical signals of the body of the subject so as to determine blood volume or blood volume rate, e.g., stroke volume, cardiac output, brain intra luminal blood volume and the like.
Heart diseases are major causes of morbidity and mortality in the modern world. Generally, heart diseases may be caused by (i) a failure in the autonomic nerve system where the impulses from the central nervous system control to the heart muscle fail to provide a regular heart rate and/or (ii) an insufficient strength of the heart muscle itself where even though the patient has a regular heart rate, its force of contraction is insufficient. Either way, the amount of blood or the rate at which the blood is supplied by a diseased heart is abnormal and it is appreciated that an assessment of the state of a patient's circulation is of utmost importance.
The simplest measurements, such as heart rate and blood pressure, may be adequate for many patients, but if there is a cardiovascular abnormality then more detailed measurements are needed.
Cardiac output (CO) is the volume of blood pumped by the heart during a time interval, which is typically taken to be a minute. Cardiac output is the product of heart rate (HR) and the amount of blood which is pumped with each heartbeat, also known as the stroke volume (SV). For example, the stroke volume at rest in the standing position averages between 60 and 80 ml of blood in most adults. Thus, at a resting heart rate of 80 beats per minute the resting cardiac output varies between 4.8 and 6.4 L per min.
A common clinical problem is that of hypotension (low blood pressure); this may occur because the cardiac output is low and/or because of low systemic vascular resistance. This problem can occur in a wide range of patients, especially those in intensive care or postoperative high dependency units. In these high risk patients, more detailed monitoring is typically established including measuring central venous pressure via a central venous catheter and continuous display of arterial blood pressure via a peripheral arterial catheter.
In addition to the above measurements, the measurement of cardiac output is extremely important For example, when combined with arterial pressure measurements, cardiac output can be used for calculating the systemic vascular resistance. The measurement of cardiac output is useful both for establishing a patient's initial cardiovascular state and for monitoring the response to various therapeutic interventions such as transfusion, infusion of inotropic drugs, infusion of vasoactive drugs (to increase or reduce systemic vascular resistance) or altering heart rate either pharmacologically or by adjusting pacing rate.
Several methods of measuring cardiac output are presently known. One such method is known as the Fick method, described by Adolf Fick in 1870. This method is based on the observation that the amount of oxygen picked up by the blood as it passes through the lungs is equal to the amount of oxygen taken up by the lungs during breathing. In Fick's method, one measures the amount of oxygen taken up by the body during respiration and the difference in oxygen concentration between venous and arterial blood and uses these measurements to calculate the amount of blood pumped through the lungs which is equal to the cardiac output. More specifically, in Fick's method the cardiac output equals the ratio between the oxygen consumption and the arteriovenous oxygen content difference.
Oxygen consumption is typically measured non-invasively at the mouth, while the blood concentrations are measured from mixed venous and peripheral arterial blood drawings. Oxygen consumption is derived by measuring the volume of an expired gas over a certain period of time and the difference in oxygen concentration between the expired gas and the inspired gas.
The Fick method suffers from many drawbacks. First, accurate collection of the gas is difficult unless the patient has an endotracheal tube because of leaks around a facemask or mouthpiece. Second, the analysis of the gas, which is straightforward if the inspired gas is air, is problematic for oxygen enriched air. Third, the arteriovenous oxygen content difference presents a further problem in that the mixed venous (i.e., pulmonary arterial) oxygen content has to be measured and therefore a pulmonary artery catheter is needed to obtain the sample, which may cause complications to the patient.
The Fick principle can also be applied with CO2 instead of oxygen, by measuring CO2 elimination which can be determined more easily as compared to oxygen consumption With this variant of Fick's method, cardiac output is proportional to the change in CO2 elimination divided by the change in end tidal CO2 resulting from a brief rebreathing period. These changes are accomplished and measured by a sensor, which periodically adds a rebreathing volume into the breathing circuit Although this method improves the ability to perform accurate measurements of gas, it still suffers from most of the above limitations, in particular the limitation related to leaks around the facemask.
Another method is by transoesophageal echocardiography (TOE) which provides diagnosis and monitoring of a variety of structural and functional abnormalities of the heart. TOE is used to derive cardiac output from measurement of blood flow velocity by recording the Doppler shift of ultrasound reflected from the red blood cells. The time velocity integral, which is the integral of instantaneous blood flow velocities during one cardiac cycle, is obtained for the blood flow in a specific site (e.g., the left ventricular outflow tract). The time velocity integral is multiplied by the cross-sectional area and the heart rate to give cardiac output. Besides being very inaccurate, the method has the following disadvantages: (i) the system may only be operated by a skilled operator; (ii) due to the size of the system's probe, heavy sedation or anaesthesia is needed; (iii) the system is expensive; and (iv) the probe cannot be configured to provide continuous cardiac output readings without an expert operator being present.
U.S. Pat. No. 6,485,431 discloses a relatively simple method in which the arterial pressure, measured by a pressure cuff or a pressure tonometer, is used for calculating the mean arterial pressure and the time constant of the arterial system in diastole. The compliance of the arterial system is then determined from a table and used for calculating the cardiac output as the product of the mean arterial pressure and compliance divided by a time constant This method, however, is very inaccurate and it can only provide a rough estimation of the cardiac output.
An additional method of measuring cardiac output is called thermodilution. This method is based on a principle in which the cardiac output can be estimated from the dilution of a bolus of saline being at a different temperature from the blood. The thermodilution involves an insertion of a fine catheter into a vein, through the heart and into the pulmonary artery. A thermistor, mounted on the tip of the catheter senses the temperature in the pulmonary artery. A bolus of saline (about 5 ml. in volume) is injected rapidly through an opening in the catheter, located in or near to the right atrium of the heart. The saline mixes with the blood in the heart and temporarily depresses the temperature in the right atrium. Two temperatures are measured simultaneously the blood temperature is measured by the thermistor sensor on the catheter and the temperature of the saline to be injected is typically measured by means of a platinum temperature sensor. The cardiac output is inversely related to the area under the curve of temperature depression.
The placement of the catheter into the pulmonary artery is expensive and has associated risk including: death; infection; hemorrhage; arrhythmias; carotid artery, thoracic duct, vena caval, tracheal, right atrial, right ventricular, mitral and tricuspid valvular and pulmonary artery injury. Little evidence suggests that placement of a pulmonary artery catheter improves survival and several suggest an increase in morbidity and mortality.
A non-invasive method, known as thoracic electrical bioimpedance, was first disclosed in U.S. Pat. No. 3,340,867 and has recently begun to attract medical and industrial attention [U.S. Pat. Nos. 3,340,867, 4,450,527, 4,852,580, 4,870,578, 4,953,556, 5,178,154, 5,309,917, 5,316,004, 5,505,209, 5,529,072, 5,503,157, 5,469,859, 5,423,326, 5,685,316, 6,485,431, 6,496,732 and 6,511,438; U.S. patent application Ser. No. 20020193689]. The thoracic electrical bioimpedance method has the advantages of providing continuous cardiac output measurement at no risk to the patient.
A typical bioimpedance system includes a tetrapolar array of circumferential band electrodes connected to the subject at the base of the neck and surrounding the circumference of the lower chest, at the level of the xiphoid process. When a constant magnitude alternating current flows through the upper cervical and lower thoracic band electrodes, a voltage, proportional to the thoracic electrical impedance (or reciprocally proportional to the admittance), is measured between the inner cervical and thoracic band electrodes. The portion of the cardiac synchronous impedance change, temporally concordant with the stroke volume, is ascribed solely and uniquely to volume changes of the aorta during expansion and contraction over the heart cycle.
A major disadvantage of existing bioimpedance systems is that the bioimpedance detectors utilized in such systems require several consecutive levels of amplifier circuits. Each amplifier circuit undesirably amplifies the input noise from signals detected in a body segment, thereby necessitating an increase in the magnitude of the measurement current to maintain a reasonable signal-to-noise ratio. Multiple amplifier circuits require substantial area on printed circuit boards and utilize numerous circuit components thereby increasing the cost and power consumption of the system. The complexity of multiple amplifier systems decreases the reliability of the systems and increases the frequency of required maintenance.
A typical printed circuit board of a bioimpedance system comprises one or more band pass filters, a half-wave rectification circuit and one or more low pass filters. One skilled in the art would appreciate that the noise level is proportional to the bandwidth of the band pass filter. As presently available band pass filters are typically characterized by a frequency ratio of about 5%, a considerable portion of the noise passes the band pass filter hence being folded into the half-wave rectification circuit. This problem is aggravated by the fact that the typical change in the impedance within the thorax is about 0.1%, thereby causing a rather low signal-to-noise ratio for such systems.
A recognized problem in bioimpedance measurement is the difficulty in separating and differentiating between cardiovascular bioimpedance signals and respiratory bioimpedance signals, where the latter are typically much larger than the former. An optimization method for increasing the efficiency of the bioimpedance measurement is disclosed in U.S. Pat. No. 4,870,578. In this method, changes in the electrical resistance caused by respiration are suppressed by a clamping circuit, synchronized with the electrical activity of the heart. The clamping circuit is timed to clamp the voltages in the measuring equipment to a baseline reference voltage in the time preceding the beginning of mechanical systole. The voltage clamping is released during the mechanical systole of the heart so that the changes in the bioimpedance caused by the pumping action of the heart during mechanical systole are measured. Although providing a certain degree of improvement to the efficiency of the measurement, this method still suffers from a rather low signal-to-noise ratio.
There is thus a widely recognized need for and it would be highly advantageous to have, a system, method and apparatus for measuring blood flow devoid of the above limitations.